Food intolerance of some kind is very common in human beings. Food allergies are also common. The majority of human beings have an intolerance of certain constituents of foods. About 5 percent of the population have reactions to ingested substances which are sufficiently serious to require medical attention. These reactions can in some instances be life-threatening. For instance, in a widely publicized case, a bride with a chronic peanut allergy died in the United States in 1990 within minutes of consuming some wedding cake that had been baked with peanut oil as a pan grease.
In recent years evidence has mounted that the basic cause of food intolerance is the absorption of substances which are normally excluded but which in susceptible individuals are absorbed by the gastrointestinal tract because of defects in the tissue which lines the digestive tract (Peters, T. F., Bjarnason, I., Canadian Journal of Gastroenterology 1988, 2: 127-132; Olaison et al., Scandinavian Journal of Gastroenterology 1990, 25: 321-328; Hollander et al., Annals of Internal Medicine, 1986, 105: 883-885).
It is becoming increasingly clear that this basic tissue defect underlies disorders of the gastrointestinal tract which can range from mild food intolerance to, in more severe cases, erosion and ultimately ulceration of the mucosa. Persons with Inflammatory Bowel Disease, which represents the more severe situation, usually also have other symptoms which relate to food allergy.
The manifestation of food allergy can involve virtually any tissue in the body. The respiratory tract is involved in many inhaled allergies affecting the eyes, ears, mouth, upper respiratory tract and the lungs. Because of the very large absorptive area in the gastrointestinal tract, it is probably the major site of absorption of offending substances. Many of the symptoms of food allergies are manifest in the digestive tract itself, but might involve any other tissues, including the brain, and, accordingly, affect behaviour.
The most successful treatment of food allergy to date is the avoidance of offending substances once they have been identified. This requires diet revision, usually involving strict restrictive measures. Most promising is the use of Elemental diets which exclude all naturally-occurring potential allergens by providing a diet of essential nutrients in their simplest form, that is, in small molecules which are readily absorbed such as food which has been digested by the action of digestive enzymes in the gut. These diets remove the offensive substances, and have proven to be highly successful in long-term treatment of patients with severe food allergies. About 80 percent of patients respond to these diets, but there is a relapse rate of about 10 percent each year.
Several patents disclose amino sugars for treatment of disorders.
U.S. Pat. No. 4,590,067, May 20, 1986, Meisner, Peritain Ltd., discloses a composition for preventing and treating periodontal disease comprising bone meal, ascorbic acid, tyrosine and either glucosamine or cysteine. N-acetyl glucosamine is not disclosed.
French Patent No. 2,473,887, Jul. 24, 1981, discloses the use of biochemical precursors of glucosamineglycans for the treatment of vascular disorders of functional or organic origin in which there is insufficient blood flow to the limbs, for asphyxic hypoxydotic symptoms, and in cosmetology, for skin defects caused by insufficient circulation to the skin. The precursors, which include N-acetylglucosamine, increase the elasticity of perivascular tissue, resulting in an increase in arterio-capillary blood flow, without having a vasodilating action.
U.S. Pat. No. 4,006,224, Feb. 1, 1977, J. F. Prudden, discloses the treatment of ulcerative colitis or regional enteritis in a mammal by administering D-glucosamine, or one of its salts. Equal or superior results to the conventional treatments of the two conditions are obtained. The dose is 20-300 mg/kg of D-glucosamine, HCl daily. In a clinical trial, a patient with Crohn's Disease that was not affected by ACTH or prednisone was given D-glucosamine, HCl subcutaneously. The symptoms stopped after several weeks of treatment.
WO A 8 702 244, N. Hendry, EP A 0178602, Peritain Ltd. and French Patent A 2016 182, Rotta Research Labratorium SpA, are of interest to this subject.
Hendry discloses a preparation for tissue growth regulation comprising (a) at least one of N-acetyl-D-glucosamine or an oligomer thereof, or a deacylated derivative thereof, or a substituted product of these compounds; (b) at least one of biotin or an analog or derivative biotin, or biologically active residue thereof; and (c) a divalent metal cation together with a pharmaceutically acceptable anion.
A key difference over the prior art is the applicant's use of N-acetyl glucosamine (NAG) as a source of amino sugar for the synthesis of molecules such as glycoproteins and glycosaminoglycans, which are rich in NAG and the synthesis of which is stimulated by NAG.
NAG is formed from glucosamine and NAG is then directly converted into other amino sugars. NAG is thus a key substance, and in the applicant's work with intestinal tissue, it was found that the formation of NAG itself from glucosamine was the slow part of the process. This necessitates the use of NAG, specifically, and not a deacetylated form, or oligomer.
NAG, moreover, is more stable than glucosamine, is a neutral substance and is readily assimilated by tissues and utilized, whereas most oligomers are not.
The proposed use of NAG is unique and differs from existing art.
An article entitled "Decreased Incorporation of .sup.14 C-Glucosamine Relative to .sup.3 H-N-Acetyl Glucosamine in the Intestinal Mucosa of Patients with Inflammatory Bowel Disease", A.F. Burton and F. H. Anderson, vol. 78, No. 1, 1983, American Journal of Gastroenterology, discloses evidence that the synthesis of glycoproteins in intestinal mucosa of patients afflicted with inflammatory bowel disease is deficient in the diseased tissues of such patients. The article discusses possible reasons for the deficiency. However, no suggestions for alleviating the deficiency are made.